1. Field of the Invention
The present invention relates to the field of methods for the treatment of shock, and more particularly to a method for treating shock by use of drugs.
2. Description of the Prior Art
The term shock is applied to a variety of pathophysiological conditions associated with hypotension. Shock is a condition of acute peripheral circulatory failure due to derangement of circulatory control or loss of circulating fluid and is marked by pallor and claminess of the skin, decreased blood pressure, feeble rapid pulse, decreased respiration, restlessness, anxiety, and sometimes unconsciousness. Some examples are hemorrhagic shock (blood loss), cardiogenic shock (heart attack), and septic shock (infection).
In spite of aggressive therapy, the morbidity and mortality rate for shock patients are quite high, in the range of 20-70%. Moreover, this has been a condition which has been extremely difficult to treat. Much research has been conducted in this field in an effort to determine the mechanism of the shock condition and methodologies for satisfactory treatment of shock after its onset.
There has been recent speculation that the body releases certain hormones or mediators which cause the low blood pressure. Many vasoactive mediators have been implicated in the pathophysiology of many shock states including endotoxic shock. The mediators which have received much attention in endotoxic shock have been the opioids, prostanoids, histamine, kinins, serotonin, VIP, etc. However, what has yet to be established is the relative hemodynamic contribution of each of these mediators in a given shock model.
Some drugs are currently being promoted for use in the treatment of shock. Previously, the use of a massive dose of glucocorticoids in a patient with septic shock was being employed. The Food and Drug Administration recently reviewed the indications for the use of corticosteroids in septic shock, in particular for a drug methylprednisolone sodium succinate, and decided to remove septic shock from the product insert as an indication for the use of high doses. The use of this and related drugs for the treatment of shock is discussed in an article entitled "Septic Shock and Corticosteroids," John N. Sheagren, M.D., appearing in The New England Journal of Medicine, pp. 456-7, Aug. 20, 1981.
It has previously been demonstrated that the cyclo-oxygenase inhibitor, ibuprofen, given 60 minutes after endotoxin administration could improve hemodynamics but not survival over control animals in a canine endotoxic shock model. A paper on this subject entitled "The Effects of Different Vasoactive Mediator Antagonists on Endotoxic Shock in Dogs I" was presented at the Fifth Annual Conference on Shock, at Smugglers' Notch, Vermont on June 9-11, 1982.
A method for the treatment of shock is described in U.S. Pat. No. 4,267,182, issued to Holaday on May 12, 1981. This method includes the administration to the patient of any of a number of drugs including naloxone, naltrexone, nalorphine, diprenorphine, levallorphan, pentazocine, metazocine, cyclazocine, etazocine and the acid addition salts thereof. Each of these drugs is indicated as a narcotic antagonist drug.
The present invention relates to the use of benoxaprofen for the treatment of shock. Benoxaprofen is a known anti-inflammatory drug which has been available from Eli Lilly & Co. of Indianapolis, Indiana for use in the treatment of arthritis. The therapeutic method for treating rheumatoid arthritis by the administration of benoxaprofen and aspirin is disclosed in U.S. Pat. No. 4,355,029, issued to Ridolfo on Oct. 19, 1982. Other anti-inflammatory drugs and their use are described in U.S. Pat. Nos. 4,282,214, issued to Flora on Aug. 4, 1981; 4,185,100, issued to Marvel on Jan. 22, 1980; 4,142,054, issued to Amin on Feb. 27, 1979; 4,135,051, issued to Walker on Jan. 16, 1979; and 4,107,439, issued to Salmond on Aug. 15, 1978.
Despite the research conducted in this field, there has remained a strong need for a method for the treatment of shock to both improve hemodynamics and survival. Although various drugs have been investigated for this purpose, the results to date have not been highly successful.